P1277: MUTATIONAL LANDSCAPE AND COPY NUMBER ALTERATIONS IN TESTICULAR LARGE B-CELL LYMPHOMA
Authors: C. López, A. Rivas-Delgado, F. Nadeu, M. Grau, A. Rivero, J. Boschs-Schips, M. Alcoceba, G. Tapia, L. Luizaga, C. Bárcena, N. Kelleher, M. Pablo, O. Balague, G. Frigola, N. Villamor, L. Magnano, T. Baumann, A. Muntañola, J. M. Sancho-Cia, A. M. García-Sancho, E. Gonzalez Barca, F. Climent, E. Campo, E. Giné, A. López-Guillermo, S. Beà
Journal: HemaSphere (2022)

Background: Testicular large B-cell lymphoma (T-LBCL) is an infrequent and aggressive lymphoma accounting for 1-2% of all non-Hodgkin’s lymphomas. T-LBCL develops in an immune privileged site behind the blood-testis barrier and has a molecular profile similar to primary central nervous system lymphoma (PCNSL). Around 75% of T-LBCL are of ABC subtype and display frequent genetic alterations of BCR signaling (CARD11, MYD88 and CD79B). Nevertheless, comprehensive molecular studies in large series of T-LBCL and comparison with nodal ABC-DLBCL or PCNSL are still missing. Aims: Herein we aimed: i) to characterize the genomic profile of T-LBCL to investigate if they are all molecularly homogeneous and to determinate if they could belong to the same entity to PCNSL; ii) to analyze the clinical features and outcome of a series of T-LBCL. Methods: We collected 63 patients with T-LBCL diagnosed between 2002 and 2021. DNA was extracted from formalin-fixed paraffin-embedded tissue biopsies. Copy number alterations (CNA) were studied using OncoScanTM CNV FFPE arrays (Thermofisher) (n=40) and gene mutations by a B-cell malignancy-oriented targeted next generation sequencing (NGS) panel capturing 121 genes (SureSelectXT, Agilent Technologies) (n=37). The genomic status of BCL2, BCL6, and MYC locus was investigated by FISH (n= 50). Cell-of-origin (COO) was assessed by immunochemistry (Hans algorithm) and/or digital expression (Lymph2Cx assay, Nanostring technologies). Results: Median age at diagnosis was 70 (30-89) years, 67% had stages I/II, and 73% low- or low-intermediate-risk IPI. All but five patients received first-line treatment with immunochemotherapy, followed by radiotherapy in 62%. Complete response rate was 80%. Progression-free survival and overall survival at 5 years were 49% (95% CI: 36-65) and 51% (95% CI: 40-69), respectively. Eighty-four percent (45/53) showed a non-GCB phenotype by Hans algorithm and 71% ABC subtype by gene expression. Preliminary data showed mutations in MYD88L265P (60%), PIM1 (57%), CD79B (54%), KMT2D (49%), OSBLP10 (41%), and TBL1XR1 (32%). Thirty-two percent of the cases had concomitant mutations in MYD88L265P, CD79B, and PIM1. MYC, BCL2, and BCL6 rearrangements were observed in 8%, 4%, and 38% cases, respectively. Two cases showed MYC and BCL6 rearrangement simultaneously. We detected CNA in all samples with a median of 13.5 alterations per case (range 1-43), including a median of 6 gains (0-24), 6 losses (0-28), and 2 copy neutral loss of heterozygosity (CN-LOH) (0-8). The most frequent CNA were trisomy 18 (33%); gains of 1q (43%), 3 (35%), 6p (28%), 9p13.2 (29%), 18q (30%), and 19q13-q14 (50%); and focal losses of 9p21.3 (CDNK2A/B) (73%), 6q21 (PRDM1) (68%), as well as larger losses of 6q22.31-q24.3 (TNFAIP3) (63%), and 17p (TP53) (20%), CN-LOH of 9p region was recurrent in 35% of cases. Loss of 6p22 (HLA) previously described in PCNSL, was detected in 12.5% of the T-LBCL cases. Summary/Conclusion: Although these data warrant further investigation, we identified that T-LBCL is a poor-risk type of DLBCL with mainly ABC subtype and peculiar genetic characteristics.